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Abstract

Background and Aim: The prevalence of type-2 diabetes (T2D) has doubled in the last three decades and is still rising at an alarming rate, thereby posing a major challenge to global health. MicroRNAs (miRNAs) are a class of short RNAs, which play an important role in regulating physiological processes in diabetes. These small RNAs post-transcriptionally suppress mRNA target expression and, therefore, modulation of specific miRNAs may prove to be a promising strategy to treat diabetes. However, the potential roles of the different microRNAs in the eitiology of diabetes and diabetes-related complications are not yet completely understood. In the present study, we aimed to explore the role of miR221/ 222 in diabetes. Materials and Methods: Mouse microvascular endothelial cells (MMECs) were cultured for 48 hours under conditions designed to mimic the mileu of type 2 diabetic mice: normal glucose (NG=11mM) and high glucose (HG=40mM). The levels of miRNA221/222 expression were then analysed by real-time PCR. MMECs were transfected with miR221/222 inhibitors and mir221/222 mimics and then cells were exposed to normal/ high glucose in the presence or absence of metformin. Expression of miRNA 221/222 were again analysed and compared. The effects of miR 221/222 expression on eNOS, phospho-eNOS and eNOS monomer/dimer protein levels were determined through western blotting. Results: We found that exposure to high levels of glucose, which mimics hyperglycaemia conditions, induced expression of miR-221 and miR-222. Treatment of metformin partially restored this HG-induced high expression of miRNA. Moreover, metformin showed an additive effect with miR221/222 inhibitors to inhibit miR 221/222 expression in hyperglycaemic condition. Furthermore, we observed that protein levels of total eNOS and phospho-eNOS decreases in HG in comparison with NG. The eNOS/P-eNOS protein levels were restored upon inhibition of miR221/222, thus indicating correlation of these micro-RNAs with eNOS signalling. Results were inversely validated by using miR mimics (overexpression). Conclusion: These findings suggest that miR221/222 may offer a new therapeutic strategy for treatment of endothelial dysfunction in diabetic patients or may work as a therapeutic modulator. The project is supported by UREP 13-116-3-024

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/content/papers/10.5339/qfarf.2013.BIOP-0147
2013-11-20
2020-09-27
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http://instance.metastore.ingenta.com/content/papers/10.5339/qfarf.2013.BIOP-0147
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